ABSTRACT The primary role of Core A ? ?Systems Biology and Gene Networks? ? is to explore in a predictive fashion the molecular and network-based similarities and differences between asthma and COPD. Networks provide frameworks for deriving information from a set of relationships among entities in the program project. We aim to develop tools to identify the disease modules for asthma and COPD, and the molecular relationships between them. The work will initially rely on the data already collected by the PPG investigators, leading to a first round of mechanistic predictions. These predictions will drive the design of subsequent experimental work and data collection, iteratively improving the Core's predictive power. Core A has two specific aims: Aim 1: Construct the network infrastructure to predict the disease module relying on data collected by the PPG Projects and Cores. The goal is to develop and improve on the existing tools to identify the disease module for asthma and COPD, and to offer an initial set of experimentally testable predictions. Aim 2: Iteratively enhance the predictive value of the disease module by overlaying data collected by the PPG Projects and Cores. We plan to explore the network-based relationships between asthma and COPD by identifying common pathways, genes and potentially common disease mechanisms. Core A will apply network analysis support at different levels: (1) selection and prioritization of the variants and genes associated with airflow obstruction from Project 1; (2) integrating different levels of genomics and transcriptomics data associated with asthma and COPD with the molecular interaction networks (interactome) from Project 2; and (3) identifying and interpreting epigenetic changes (methylation and miRNA) associated with asthma and COPD from Project 3 by integration with protein interactome models. The networks of interactions will serve as a scaffold for information to extract global and local graph theory properties to inform about the initial seed gene choices and about the different ?omics? data in Projects 1, 2 and 3.